Summary Annually, one million children die of TB and 25% of the global TB cases occur in children, adolescents and young adults. Tibetan refugees in India have extraordinarily high TB rates. In 2017-18, we observed a TB case and infection prevalence of 916/100,000 and ~20%, respectively, for schoolchildren residing in Tibetan boarding schools in India. More than 60% of the total Tibetan TB cases occur in the schools and monasteries. Despite this burden, understanding is limited of the epidemiology of TB in the Tibetan population and strategies for its prevention. Zero TB in Tibetan Kids (ZTBK) is a fully funded and established public health program of the Johns Hopkins University, Tibetan Delek Hospital, and the Department of Health of the Central Tibetan Administration that aims to eliminate TB for Tibetan children and adolescents through a multipronged approach of screening, treatment and preventive therapy. With ongoing support, the ZTBK is now scaled up to cover ~40,000 people in schools and monasteries across 3 states through 2022. In this mobile program, the entire institution is screened for TB using symptom, tuberculin skin test, chest X-ray, and Xpert. All Xpert positive and suspected specimens are sent to the Hinduja Lab, Mumbai, for culture and drug susceptibility testing. Culture positive isolates are stored at the Hinduja for whole genome sequencing (WGS). I will use data from this ZTBK initiative to study TB epidemiology, transmission, and preventive therapy outcomes for children, adolescents, and young adults in the Tibetan schools, monasteries, and nunneries in Himachal Pradesh state of India. For Aim 1, I will characterize TB infection and disease and study the epidemiologic risk factors. For Aim 2, I postulate that most TB transmission in the congregate settings happen through recent transmission. I will study TB transmission by analyzing single nucleotide polymorphisms in the WGS data and relate the genomic clusters with epidemiological links. Using geospatial analysis, I will relate the transmission data with spatial coordinates for a complete understanding of the transmission dynamics. For Aim 3, I will test the postulate that receiving preventive therapy in the congregate settings will lead to a sustained lower risk of disease over five-years of follow-up period. Through the aims, I will study the characteristics of subclinical TB disease and its transmissibility. The results will inform TB preventive therapy strategies and targeted interventions to interrupt transmission at the facility/community levels and have broad applicability to children and young adults in schools and other settings, globally. The training goals I have identified that include spatial analysis and analysis of WGS data will enable me to accomplish the aims of the study. The opportunity for mentorship, training, and research through this award will give me the knowledge, experience, and expertise to develop an R01 proposal for a multicenter study on TB transmission and preventive therapy that will allow me to become an independent investigator.